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Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice

The primary function of the small intestine (SI) is to absorb nutrients to maintain whole-body energy homeostasis. Enterocytes are the major epithelial cell type facilitating nutrient sensing and uptake. However, the molecular regulators governing enterocytes have remained undefined. Here, we identi...

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Autores principales: Cosovanu, Catalina, Resch, Philipp, Jordan, Stefan, Lehmann, Andrea, Ralser, Markus, Farztdinov, Vadim, Spranger, Joachim, Mülleder, Michael, Brachs, Sebastian, Neumann, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9486084/
https://www.ncbi.nlm.nih.gov/pubmed/36121416
http://dx.doi.org/10.1084/jem.20220233
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author Cosovanu, Catalina
Resch, Philipp
Jordan, Stefan
Lehmann, Andrea
Ralser, Markus
Farztdinov, Vadim
Spranger, Joachim
Mülleder, Michael
Brachs, Sebastian
Neumann, Christian
author_facet Cosovanu, Catalina
Resch, Philipp
Jordan, Stefan
Lehmann, Andrea
Ralser, Markus
Farztdinov, Vadim
Spranger, Joachim
Mülleder, Michael
Brachs, Sebastian
Neumann, Christian
author_sort Cosovanu, Catalina
collection PubMed
description The primary function of the small intestine (SI) is to absorb nutrients to maintain whole-body energy homeostasis. Enterocytes are the major epithelial cell type facilitating nutrient sensing and uptake. However, the molecular regulators governing enterocytes have remained undefined. Here, we identify c-Maf as an enterocyte-specific transcription factor within the SI epithelium. c-Maf expression was determined by opposing Noggin/BMP signals and overlapped with the zonated enrichment of nutrient transporters in the mid-villus region. Functionally, enterocytes required c-Maf to appropriately differentiate along the villus axis. Specifically, gene programs controlling carbohydrate and protein absorption were c-Maf–dependent. Consequently, epithelial cell–specific c-Maf deletion resulted in impaired enterocyte maturation and nutrient uptake, including defects in the adaptation to different nutrient availability. Concomitantly, intraepithelial lymphocytes were less abundant, while commensal epithelial cell–attaching SFB overgrew in a c-Maf–deficient environment, highlighting the close interdependence between the intestinal epithelium, immune system, and microbiota. Collectively, our data identified c-Maf as a key regulator of SI enterocyte differentiation and function, essential for nutrient, immune, and microbial homeostasis.
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spelling pubmed-94860842023-03-19 Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice Cosovanu, Catalina Resch, Philipp Jordan, Stefan Lehmann, Andrea Ralser, Markus Farztdinov, Vadim Spranger, Joachim Mülleder, Michael Brachs, Sebastian Neumann, Christian J Exp Med Brief Definitive Report The primary function of the small intestine (SI) is to absorb nutrients to maintain whole-body energy homeostasis. Enterocytes are the major epithelial cell type facilitating nutrient sensing and uptake. However, the molecular regulators governing enterocytes have remained undefined. Here, we identify c-Maf as an enterocyte-specific transcription factor within the SI epithelium. c-Maf expression was determined by opposing Noggin/BMP signals and overlapped with the zonated enrichment of nutrient transporters in the mid-villus region. Functionally, enterocytes required c-Maf to appropriately differentiate along the villus axis. Specifically, gene programs controlling carbohydrate and protein absorption were c-Maf–dependent. Consequently, epithelial cell–specific c-Maf deletion resulted in impaired enterocyte maturation and nutrient uptake, including defects in the adaptation to different nutrient availability. Concomitantly, intraepithelial lymphocytes were less abundant, while commensal epithelial cell–attaching SFB overgrew in a c-Maf–deficient environment, highlighting the close interdependence between the intestinal epithelium, immune system, and microbiota. Collectively, our data identified c-Maf as a key regulator of SI enterocyte differentiation and function, essential for nutrient, immune, and microbial homeostasis. Rockefeller University Press 2022-09-19 /pmc/articles/PMC9486084/ /pubmed/36121416 http://dx.doi.org/10.1084/jem.20220233 Text en © 2022 Cosovanu et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Report
Cosovanu, Catalina
Resch, Philipp
Jordan, Stefan
Lehmann, Andrea
Ralser, Markus
Farztdinov, Vadim
Spranger, Joachim
Mülleder, Michael
Brachs, Sebastian
Neumann, Christian
Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice
title Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice
title_full Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice
title_fullStr Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice
title_full_unstemmed Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice
title_short Intestinal epithelial c-Maf expression determines enterocyte differentiation and nutrient uptake in mice
title_sort intestinal epithelial c-maf expression determines enterocyte differentiation and nutrient uptake in mice
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9486084/
https://www.ncbi.nlm.nih.gov/pubmed/36121416
http://dx.doi.org/10.1084/jem.20220233
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